Phase 3 Adductor Canal Block With EXPAREL in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty

A Phase 3, Randomized, Double-Blind, Multicenter, Active-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL Admixed With Bupivacaine Hydrochloric Acid (HCl) vs. Bupivacaine HCl Administered Via Adductor Canal Block for Postsurgical Analgesia in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty

The purpose of the study is to compare magnitude of postsurgical analgesic effect in different groups following a single dose of study drug when administered via adductor canal block in subjects undergoing primary unilateral total knee arthroplasty.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis; Pain Management
• Intervention / Treatment: Drug: bupivacaine liposome injectable suspension; Drug: Bupivacaine Hydrochloride

Detailed Description

This is a Phase 3, multicenter, randomized, double-blind, active-controlled study in approximately 160 subjects undergoing primary unilateral TKA under spinal anesthesia. The study will have 2 cohorts, enrolling in parallel.

Cohort 1 -Pharmacokinetics (PK), pharmacodynamics (PD), Efficacy, and Safety, Cohort 2 -Efficacy and Safety

An adaptive study design will be used in this study. An interim analysis to evaluate the sample size assumptions and evaluate futility will occur when a total of approximately 80 subjects (40 subjects in each arm) combined from either Cohort 1 or Cohort 2 have enrolled and provided complete assessment data for the primary efficacy outcome.

The time from study drug administration until the end of participation is Post-operative day (POD) 14 (±3 days). Therefore, subjects may participate in the study for up to 62 days.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Ohio
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center, LLC
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Surgical Hospital
    • Carrollton, Texas, United States, 75006
      • HD Research- Legent Orthopedic Hospital
    • San Antonio, Texas, United States, 78240
      • Endeavor Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female, ages 18 or older at screening.
2. Indicated to undergo primary unilateral total knee arthroplasty under spinal anesthesia.
3. Primary indication for TKA is degenerative osteoarthritis of the knee.
4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
5. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
6. Body Mass Index (BMI) ≥18 and <40 kg/m2.

Exclusion Criteria:

1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs).
2. Planned concurrent surgical procedure (e.g., bilateral TKA).
3. Undergoing unicompartmental TKA or revision TKA.
4. Concurrent painful physical condition (e.g., arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the knee surgery and which, in the Investigator's opinion, may confound the post dosing assessments.
5. Inadequate sensory function below the knee as assessed by the Investigator.
6. History of contralateral TKA within 1 year.
7. Previous open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
8. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
9. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.
10. Previous participation in an EXPAREL study.
11. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.
12. Currently pregnant, nursing, or planning to become pregnant during the study.
13. Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction, or other conditions that would constitute a contraindication to participation in the study.
14. Currently on a neuromodulating agent (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta], etc.)].
15. Current use of systemic glucocorticoids within 30 days of randomization in this study.
16. Use of dexmedetomidine HCl (Precedex®) or clonidine within 3 days of study drug administration.
17. Any use of marijuana [including Tetrahydrocannabinol (THC) and Cannabidiol (CBD)] within 30 days prior to randomization, or planned use during the course of the study.
18. Chronic opioid use (average ≥30 oral morphine equivalents/day) within 30 days prior to randomization.

Given the coronavirus disease 2019 (COVID-19) pandemic, if there is a concern about a subject's recent or potential exposure to COVID-19, or if the subject is not medically fit/cleared for surgery due to suspected COVID-19 illness/symptoms, the subject must be excluded per Exclusion criterion #13.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: EXPAREL admix arm; subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl	Drug: bupivacaine liposome injectable suspension; Adductor canal block with EXPAREL; Other Names: EXPAREL
Active Comparator: Cohort 1: Bupivacaine HCl arm; subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline	Drug: Bupivacaine Hydrochloride; Adductor Canal Block with bupivacaine HCl
Experimental: Cohort 2: EXPAREL admix arm; subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl	Drug: bupivacaine liposome injectable suspension; Adductor canal block with EXPAREL; Other Names: EXPAREL
Active Comparator: Cohort 2: Bupivacaine HCl arm; subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline	Drug: Bupivacaine Hydrochloride; Adductor Canal Block with bupivacaine HCl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NRS Scores Through 96 Hours Post-surgery	The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point: 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.	0 to 96 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postsurgical Opioid Consumption Through 96 Hours Post-surgery	Total postsurgical opioid consumption in mg oral morphine equivalents (OMED) from 0 to 96 hours post-surgery.	0 to 96 hours post-surgery
Time to First Opioid	Time to first opioid consumption post-surgery	0 to 96 hours post-surgery
NRS Scores	Worst and average NRS pain intensity scores at 24h, 48h, 72h and 96h from the end of surgery Worst and average pain intensity scores on a numeric rating scale ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours. Mean scores at each timepoint are provided. The total range is 0 (no pain) to 10 (worst possible pain). Higher values on the scale represent worst outcome	0-24hours, 24-48hours, 48-72hours, 72-96hours

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Investigators: Study Director: Gary Nevins, Pacira Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): July 11, 2022

Study Registration Dates

• First Submitted: November 15, 2021
• First Submitted That Met QC Criteria: November 29, 2021
• First Posted (Actual): December 1, 2021

Study Record Updates

• Last Update Posted (Actual): October 24, 2024
• Last Update Submitted That Met QC Criteria: October 22, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: analgesic; bupivacaine; knee arthroplasty; Adductor Canal Block; TKA; EXPAREL
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Arthritis; Joint Diseases; Rheumatic Diseases; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Peripheral Nervous System Agents; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Sensory System Agents; Bupivacaine
• Other Study ID Numbers: 402-C-335

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No